导读：苯达莫司汀—08年美国上市的白血病特药。临床研究显示，盐酸苯达莫司汀单药或联合其他药物治疗多种血液系统恶性肿瘤或实体瘤疗效显示，于2008年或美国批准用于治疗慢性淋巴细胞性白血病以及在美罗华或含利妥昔单抗方案治疗过程中，或者治疗6个月内，病情仍然进展的惰性B细胞非霍奇金淋巴瘤。

盐酸苯达莫司汀的化学名为4-[5-[双（2-氯乙基）氨基]-1-甲基苯并咪唑-2-基]丁酸盐酸盐。早在上世纪60年代，盐酸苯达莫司汀即由前东德研制而成，并被广泛应用，但直到冷战结束，该药才在欧洲进行了多项单药或联合其他药物治疗多种血液系统恶性肿瘤或实体瘤的临床研究，疗效非常可观。

到目前为止，盐酸苯达莫司汀单药或联合治疗方案已被欧美临床指南指定为多种血液系统恶性肿瘤的一线或二线治疗选择。2003年，盐酸苯达莫司汀在德国上市，商品名为“Ribomustin”。在美国上市的盐酸苯达莫司汀商品名为“Treanda”，由Cephalon公司提出上市申请。

2008年3月，FDA首先批准盐酸苯达莫司汀用于治疗慢性淋巴细胞性白血病（CLL）。同年10月，FDA又批准了该药的第2个适应证，即在利妥昔单抗（rituximab，美罗华）或含利妥昔单抗方案治疗过程中，或者治疗6个月内，病情仍然进展的惰性B细胞非霍奇金淋巴瘤（NHL）患者。

【适应症】慢性淋巴细胞性白血病（CLL）；在利妥昔单抗（美罗华）或含利妥昔单抗方案治疗过程中，或者治疗6个月内，病情仍然进展的惰性B细胞非霍奇金淋巴瘤（NHL）。

【剂量及用药】苯达莫司汀冻干粉针呈白色至灰白色，规格为100mg/支。该药储存温度不应超过30℃，避光保存，使用前临时配制。

配制流程：该药每100mg须先溶于20ml无菌注射用水，充分振摇直到完全溶解成澄清、无色或淡黄色溶液，溶解时间一般不超过5分钟，溶解后浓度为5mg/ml。在溶解后30分钟之内，根据需要抽取适量苯达莫司汀水溶液，转移至500ml氯化钠注射液（0.9%）或葡萄糖氯化钠注射液（2.5%/0.45%）中，并确保苯达莫司汀在注射液中的最终浓度在0.2～0.6mg/ml之间。配制好的注射液可在2～8℃冷藏保存24小时，或在室温及自然光下保存3小时。

苯达莫司汀治疗CLL时，以28天为一个治疗周期，一般需要6个治疗周期。在每个治疗周期的第一天和第二天给药，推荐剂量为100mg/m2。该药经静脉滴注给药，每次给药时间不应少于30分钟。

苯达莫司汀治疗NHL时，以21天为一个治疗周期，一般需要8个治疗周期。在每个治疗周期的第一天和第二天给药，推荐剂量为120mg/m2。每次给药时间不应少于60分钟。

【禁忌症】对盐酸苯达莫司汀及甘露醇过敏者禁用。

【药物相互作用】与CYP1A2抑制剂（如氟伏沙明，环丙沙星等）合用时，有可能会升高苯达莫司汀血浓度，并使其代谢物M3和M4浓度降低；与CYP1A2诱导剂（如奥美拉唑，抽烟等）合用时，有可能会降低苯达莫司汀血浓度，并使其代谢物M3和M4浓度升高。

【不良反应】苯达莫司汀常见不良反应包括恶心、呕吐、腹泻、疲乏、虚弱、皮疹、搔痒、一些感染症状和体征（如持续咽喉疼痛、发热和寒战）、容易碰伤/出血以及口腔溃疡等；严重不良反应可能还有骨髓抑制、肿瘤溶解综合征等。苯达莫司汀可能引起轻微或严重过敏反应，患者在给药过程中或给药后初期可能出现皮疹、面部肿胀、呼吸困难等过敏症状。苯达莫司汀可能对胎儿造成影响，因此，女性治疗过程中及治疗后3个月内，应采取适当避孕措施及停止哺乳。

【药理及药代动力学】盐酸苯达莫司汀的确切作用机制尚不十分清楚，但已知该药是携带一个嘌呤样苯并咪唑环的氮芥衍生物，兼具烷化剂和嘌呤类似物（抗代谢药）的双重作用机制。盐酸苯达莫司汀能通过几种不同途径导致细胞死亡，而且对静止期和分裂期细胞均有效。

盐酸苯达莫司汀血浆蛋白结合率为94%～96%，数据显示该药一般不会与其他高蛋白结合药物相互置换。盐酸苯达莫司汀平均稳态分布容积约为25L，其全血/血浆浓度比为0.84～0.86。盐酸苯达莫司汀主要通过水解反应进行代谢，同时形成细胞毒性较低的代谢产物。该药经CYP1A2代谢途径可产生M3和M4两种活性代谢产物，但两者血浆浓度只分别相当于母体化合物的1/10和1/100，因此，可以推测苯达莫司汀的细胞毒性作用主要来自于其本身，而非其代谢物。
Treanda
Generic Name: bendamustine (BEN da MUS teen)
Brand Names: Treanda

What is Treanda?
Treanda (bendamustine) is a cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body.

Treanda is used to treat chronic lymphocytic leukemia. It is also used to treat indolent B-cell non-Hodgkin lymphoma after other medications have been tried without successful treatment of this condition.

Treanda may also be used for other purposes not listed here.

Important information about Treanda
You should not receive Treanda if you are allergic to bendamustine or mannitol (Osmitrol). Do not receive Treanda if you are pregnant. It could harm the unborn baby.

Before you receive Treanda, tell your doctor if you have a weak immune system, fever or other signs of infection, a metabolic disorder or electrolyte imbalance, liver or kidney disease, or if you smoke.

Tell your caregiver right away if you have a fever, chills, itching, or skin rash during or shortly after the Treanda injection.

Other serious side effects to tell your doctor about include fever, chills, cough, sore throat, feeling short of breath, pale skin, easy bruising or bleeding, unusual weakness, severe skin rash, weak pulse, muscle weakness, fast or slow heart rate, confusion, lower back pain, blood in your urine, urinating less than usual, or swelling, redness, or signs of where Treanda was injected.

To be sure Treanda is not causing harmful effects, your blood may need to be tested often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.

Before receiving Treanda
You should not receive Treanda if you are allergic to bendamustine or mannitol (Osmitrol).

To make sure you can safely receive Treanda, tell your doctor if you have any of these other conditions:
a weak immune system;
fever or other signs of infection;
a metabolic disorder or electrolyte imbalance;
liver disease;
kidney disease; or
if you smoke.

FDA pregnancy category D. Do not receive Treanda if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. It is not known whether bendamustine passes into breast milk or if it could harm a nursing baby. Do not receive Treanda without telling your doctor if you are breast-feeding a baby.

Some people receiving Treanda have developed certain types of cancers. It is not known whether this medication causes cancer. Talk with your doctor about the risks and benefits of using Treanda.

How is Treanda given?
Treanda is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. Treanda must be given slowly, and the IV infusion can take at least 30 minutes to complete.

Treanda is usually given for 2 days in a row every 21 to 28 days. You may receive up to 8 treatments total, depending on the condition being treated. Follow your doctor's instructions.

You may be given other medications to help prevent certain side effects of Treanda.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when the medicine is injected.

To be sure Treanda is not causing harmful effects, your blood may need to be tested often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.

What happens if I miss a dose?
Call your doctor for instructions if you miss an appointment for your Treanda injection.

What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include drowsiness, tremors, slow or shallow breathing, loss of balance or coordination, or seizure (convulsions).

What should I avoid while receiving Treanda?
Treanda may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Treanda side effects
Some people receiving a Treanda injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you have fever, chills, itching, or skin rash during or shortly after the injection. Get emergency medical help if you have any of these signs of an allergic reaction to Treanda: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Tell your caregivers at once if you have a serious side effect such as:
fever, chills, body aches, flu symptoms, sores in your mouth and throat;
pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
easy bruising or bleeding, purple or red pinpoint spots under your skin, unusual weakness;
cold symptoms such as stuffy nose, sneezing, cough, sore throat;
lower back pain, blood in your urine, urinating less than usual or not at all;
numbness or tingly feeling around your mouth;
muscle weakness, tightness, or contraction, overactive reflexes;
fast or slow heart rate, weak pulse, confusion;
dry mouth, feeling very thirsty or hot, heavy sweating or hot and dry skin;
severe blistering, peeling, and red skin rash; or
pain, swelling, redness, skin changes, or signs of infection where the medicine was injected.

Less serious Treanda side effects may include:
mild nausea, vomiting, diarrhea, constipation, or upset stomach;
swelling in your hands or feet;
headache, dizziness, drowsiness;
loss of appetite, weight loss; or
mild skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Treanda?
Tell your doctor about all other medications you use, especially:
allopurinol (Zyloprim);
carbamazepine (Carbatrol, Equetro, Tegretol);
cimetidine (Tagamet);
ciprofloxacin (Cipro);
fluvoxamine (Luvox);
omeprazole (Prilosec);
thiabendazole (Mintezol); or
a barbiturate such as butabarbital (Butisol), secobarbital (Seconal), phenobarbital (Solfoton), and others.

This list is not complete and other drugs may interact with Treanda. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?
Your doctor or pharmacist can provide more information about Treanda.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.